Nutritional and hematological determinants of immune reconstitution and development of a predictive model among virologically suppressed people living with HIV

Background Despite effective viral suppression achieved through antiretroviral therapy (ART), a substantial proportion of people living with HIV (PLWH) fail to achieve adequate immune reconstitution and remain at increased risk of adverse clinical outcomes. Methods A retrospective cohort study was conducted among PLWH in Hebei Province, China, who received long-term ART and achieved sustained virological suppression. Immune reconstitution was defined as achieving a CD4 + T cell count ≥350 cells/μL during follow-up. Kaplan–Meier analysis and Cox proportional hazards regression were performed to evaluate the dynamics of immune recovery and identify independent predictors associated with time to immune reconstitution. A prognostic model was developed and evaluated using Harrell’s concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration analysis, and 1,000-times bootstrap internal validation. Results During a median follow-up of 4.02 years (95% CI: 4.00–4.04 years), 1,651 (76.9%) participants achieved immune reconstitution, whereas 495 (23.1%) did not achieve immune reconstitution. The probability of immune recovery increased rapidly during the first year after ART initiation and subsequently plateaued. Multivariable Cox regression analysis showed that older age, advanced WHO clinical stage, and lower baseline CD4 + T cell count were independently associated with a reduced probability of immune reconstitution. In addition, overweight status (BMI ≥ 24 kg/m2; HR = 1.12, 95% CI: 1.02–1.23, p = 0.021) and higher baseline hemoglobin levels (HR = 1.004, 95% CI: 1.001–1.007, p = 0.016) were independently associated with improved immune recovery after adjustment for established clinical and immunological factors. The prediction model demonstrated good discrimination (C-index = 0.713), with time-dependent AUCs of 0.849, 0.874, and 0.850 at 1, 2, and 4 years, respectively. Calibration analysis showed good agreement between predicted and observed immune recovery probabilities. Conclusion Approximately one-quarter of virologically suppressed PLWH did not achieve immune reconstitution after long-term ART. Immune recovery occurred predominantly during the first year after ART initiation. In addition to established predictors such as age, baseline CD4 + T cell count, and WHO clinical stage, BMI and hemoglobin levels may serve as readily obtainable clinical indicators reflecting nutritional reserve and overall health status. The developed prediction model may provide a practical approach for identifying individuals with delayed immune recovery and supporting individualized clinical monitoring.